Optical imaging is a molecular and functional imaging technique, primarily used for imaging of small animals in a research setting. This technique relies upon sensitive detection of light emitted by luminescent cells, tissues, or contrast agents. Optical imaging can be used to detect certain cell types of interest within the body (for example, cells made to express luciferase for bioluminescence imaging), or to detect contrast agents localized within tissues of interest (for example molecular imaging of a targeted receptor).
Optical imaging using contrast agents typically utilizes molecules or nanoparticles bearing one or more fluorophores, typically active in the near infrared range. Typical contrast agents are injected intravascularly or intraperitoneally, and allowed to accumulate at the target site over several hours to days. A significant difficulty with previously described contrast agents relates to the time required for clearance of unbound contrast. Agents in the nanometer size range can generally distribute throughout the tissues of the body. This can cause a significant non-specific (background) signal, which can require several hours to days to be cleared by the relevant biological pathways; the duration of this clearance is known as the dwell time. A long dwell time can introduce significant inconvenience in imaging workflow, especially in a high-throughput research setting. Additionally, a long dwell period can negate the possibility of administering multiple contrast agent doses within the same imaging setting, due to the requirement that previously administered contrast be fully cleared before subsequent doses can be administered (in order to avoid signal contamination from the previous doses). This can be a problem, for example, in the context of imaging multiple molecular markers within a single patient population. A system whereby contrast agents can be rapidly cleared could significantly benefit molecular imaging workflow.
A second difficulty with previously described contrast agents relates to target specificity. As mentioned above, nano-scale contrast agents distribute throughout the entire body; intravenously administered agents of this size readily diffuse through the vascular wall and into the surrounding tissue due to the very small size of the contrast agent. Many of the molecular imaging targets of key relevance for inflammation, thrombosis, and angiogenesis are expressed on the luminal vascular endothelium or associated cells. Thus, the movement of contrast agents out of the vascular space can introduce off-target non-specific signals. A contrast agent that can be administered intravenously and remain essentially confined to the vascular lumen would enable significantly greater specificity for purely intravascular targets. The present invention overcomes these difficulties.